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Synthetic Peptides of Epstein–Barr Virus-major Envelope Glycoprotein-350/220 do not Prevent Infection in a Rabbit Epstein–Barr Virus Infection Model

Kaoru Kato, Hitoshi Sano, Keiko Nagata, Hirotsugu Sugihara, Kyosuke Kanai, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami and Kazuhiko Hayashi

Epstein–Barr virus (EBV) is a ubiquitous herpes virus that usually infects humans asymptomatically, occasionally inducing various EBV-associated diseases, including infectious mononucleosis (IM), chronic active EBV infection, and different types of malignant tumors. A history of IM is associated with a 3-fold increased risk for subsequent EBV-related Hodgkin lymphoma. In immunocompromised individuals or transplant patients, EBV presents a high risk for morbidity and mortality, although prophylactic vaccination against EBV might contribute to reduce this risk. In this study, we used a rabbit EBV infection model to determine whether vaccination with synthesized peptides based on gp350/220 sequences could effectively prevent EBV infection or decrease the rate or degree of EBV infection. Six rabbits vaccinated with EBV gp350-peptides and four controls were challenged with a minimum dose of EBV infection; EBV-DNAs or EBV-RNAs were detected in 5/6 and 4/4 rabbits, respectively. This suggested that a gp350-peptide vaccine could not prevent primary EBV infections in rabbits and indicated the presence of EBV infection routes or mechanisms in rabbits other than the gp350-CD21 interaction observed in EBV infection of human B-cells. However, this vaccine probably has the efficacy to control the viral loads in inoculated rabbits, because 5 out of 6 vaccinated rabbits showed no detectable EBV-DNA in their blood and either no or only few EBER-1-positive lymphocytes in the lymphoid tissues. This vaccine was immunogenic; however, developing other improved vaccines or adjuvants will be necessary to reduce EBV-related diseases.